Published in

Karger Publishers, Liver Cancer, 2(13), p. 119-135, 2023

DOI: 10.1159/000531458

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Recent Advances in Systemic Therapy for Advanced Intrahepatic Cholangiocarcinoma

Journal article published in 2023 by Changhoon Yoo, Jaewon Hyung, Stephen L. Chan ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

<b><i>Background:</i></b> The incidence of intrahepatic cholangiocarcinoma (IHCCA) is rising around the world. The disease is becoming a major global health issue. Conventionally, most patients with cholangiocarcinoma present with advanced disease and systemic therapy is the mainstay of treatment. This review discusses recent advances in systemic treatments for patients with IHCCA. <b><i>Summary:</i></b> The addition of durvalumab to a gemcitabine plus cisplatin regimen has significantly improved overall survival in the phase 3 TOPAZ-1 trial and is currently recommended as a standard first-line treatment. The phase 3 ABC-06 and phase 2b NIFTY trials have shown the benefit of second-line fluoropyrimidine plus oxaliplatin, and fluoropyrimidine plus nanoliposomal irinotecan, respectively. They have provided a treatment option for patients without actionable alterations who progressed to first-line therapy. For patients with actionable genomic alterations, including <i>FGFR2</i> rearrangement, <i>IDH1</i> mutation, <i>BRAF</i> mutation, and <i>ERBB2</i> amplification, targeted agents have shown encouraging efficacy in several phase 2–3 trials, and are recommended as subsequent treatments. Immune checkpoint inhibitors are being investigated for the treatment of previously treated patients, although only a small proportion of patients showed durable responses. <b><i>Key Messages:</i></b> Recent advances in systemic treatments have improved clinical outcomes in patients with advanced IHCCA. However, most patients eventually show resistance to the treatment, and tumor progression occurs within a year. Indeed, there should be further efforts to improve the outcomes of patients with advanced IHCCA.